Potassium Carbonate → 3'-Chloro-6-fluoro-2-methoxy-biphenyl

HRID 1632020Notes

Reaction equation

HRID 1632020 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][CH3:10].[Cl:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C(O)C.O.O1CCOCC1>[Cl:11][C:12]1[CH:17]=[C:16]([C:2]2[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=2[O:9][CH3:10])[CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 2734323(3-Chlorophenyl)boronic acidHCID 27793182-Bromo-3-fluoroanisole

Product 1

HCID 580203133'-Chloro-6-fluoro-2-methoxy-biphenylYield 115.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
180 °C

Procedure

To 2-bromo-3-fluoroanisole (1.0 g, 4.88 mmol), 3-chlorophenylboronic acid (0.91 g, 5.88 mmol), PPh3 (0.64 g, 2.44 mmol), K2CO3 (0.27 g, 1.95 mmol) and Pd(OAc)2 (0.13 g, 0.58 mmol) was added dioxane (8 mL), and EtOH—H2O (1:1, 4 mL). Ar gas was bubbled through the stirred reaction for 5 min. The reaction was heated at 180° C. using microwave oven (Biotage Intiator II) for 20 min. The reaction was cooled to room temperature, combined with another 0.5 g scale run, concentrated. The residue was purified by silica gel column chromatography using 1:1 dichloromethane-hexanes to afford 1.33 g (77%) 3′-chloro-6-fluoro-2-methoxy-biphenyl (I-16, R1═CH3, R2═Cl, Y═F) as a viscous liquid.

Workup

  1. customAr gas was bubbled through the stirred reaction for 5 min
  2. customfor 20 min
  3. temperatureThe reaction was cooled to room temperature
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3441c3f022064a24af1168426821c5c2
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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